A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma

NCT01730222 | Completed Phase 1

• 2 other identifiers: PACT-192012-001763-75
• Study Type: interventional
• Target: 137
• Locations: 1 country
• Sites: 1

Brief Summary

Four-drug combo yielded a statistically significant improvement in progression-free survival and overall survival compared to gemcitabine in patients with advanced pancreatic adenocarcinoma. Nab-Paclitaxel showed promising antitumor activity in patients with pancreatic cancer. Given the synergism of taxanes with gemcitabine, fluoropyrimidines and platinating agents the role of nab-Paclitaxel in a 4-drug regimen will be explored. The aim of this trial is to determine the recommended dose of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine, PAXG regimen (Phase I), and to evaluate the feasibility and the activity of the PAXG regimen in patients with stage III and IV pancreatic cancer.

Conditions

Pancreatic Cancer

Keywords

pancreatic adenocarcinoma; stage III disease; stage IV disease; chemotherapy

Outcome Measures

Primary Outcomes (3)

• first cycle toxicity for phase I part

  Dose Limiting Toxicity definition: DLT will be defined as any of the following events attributable to the administered study drugs: * Hematologic toxicity * Grade ≥ 4 neutropenia lasting 7 days or more * Grade ≥ 3 febrile neutropenia or fever of unknown origin ≥ 38.5°C * Grade 4 thrombocytopenia * Grade 3 thrombocytopenia which required transfusions * Nausea or vomiting Grade ≥ 3 nausea or vomiting despite maximal antiemetic therapy * Diarrhea Grade ≥ 3 diarrhea despite optimal management of the event * Neurological toxicity Any Grade ≥ 2 neurological toxicity * Other non-hematologic toxicity Any grade ≥ 3 toxicities or representing a shift by 2 grades from baseline (in case of abnormal baseline) * Failure to recover Failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by \> 2 weeks.

  after one month from treatment start

• progression-free survival for phase II part, stage IV patients

  rate of progression-free patients at 6 months from randomization

  after 6 months from randomization

• resectability rate for phase II part, stage III patients

  rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start

  after 4 and 6 months from treatment start

Secondary Outcomes (5)

• response rate

  every two months up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

• biochemical response rate

  every month up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

• toxicity

  every two weeks up to 26 weeks during treatment

• overall survival

  From date of trial enrolment until the date of death from any cause, assessed every two weeks up to 26 weeks during treatment; every 2-3 months afterwards up to 60 months

• Progression-free survival

  From date of trial enrolment until the date of documented progression or date of death from any cause, whichever came first, assessed every two months up to 6 months during treatment; every 2-3 months afterwards up to 60 months

Study Arms (2)

PAXG regimen

EXPERIMENTAL

cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15 every 4 weeks

Drug: cisplatin; Drug: capecitabine; Drug: gemcitabine; Drug: nab-paclitaxel

gemcitabine + nab-paclitaxel

ACTIVE COMPARATOR

gemcitabine at 1000 mg/ m2 on days 1, 8 and 15 every 4 weeks + nab-paclitaxel at 125 mg/ m2 on days 1, 8 and 15 every 4 weeks

Drug: gemcitabine; Drug: nab-paclitaxel

Interventions

cisplatin DRUG

cisplatin at 30 mg/m2 on days 1 and 15

Also known as: cisplatino TEVA

PAXG regimen

capecitabine DRUG

capecitabine at 1250 mg/ m2 days 1-28

Also known as: XELODA

PAXG regimen

gemcitabine DRUG

gemcitabine at 800 mg/ m2 on days 1 and 15 in arm A; at 1000 mg/m2 on days 1, 8 and 15 in arm B

Also known as: Gemzar

PAXG regimen; gemcitabine + nab-paclitaxel

nab-paclitaxel DRUG

nab-paclitaxel at the recommended phase II dose day 1 and 15 in arm A; at 125 mg/m2 on days 1, 8 and 15 in arm B

Also known as: abraxane

PAXG regimen; gemcitabine + nab-paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologic diagnosis of pancreatic adenocarcinoma
• Stage III or IV disease
• Age \> 17 \< 76 years
• Karnofsky Performance Status \> 50
• Measurable disease (only for phase II part)
• Adequate bone marrow (GB \> 3500/mm3, neutrophils \> 1500/mm3; platelets \> 100000/mm3; hemoglobin \> 10 g/dl), liver (total bilirubin \< 2 mg/dL; SGOT e SGPT \< 3 UNL) and kidney function (serum creatinin \< 1.5 mg/dL;)
• Written informed consent

You may not qualify if:

• previous chemotherapy
• concurrent treatment with other experimental drugs
• previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin and of other neoplasms without evidence of disease at least from 5 years
• symptomatic brain metastases
• history of interstitial lung disease
• presence of serious disease which can compromise safety (cardiac failure, previous myocardial infarction within the prior 6 months, cardiac arrhythmia, history of psychiatric disabilities)
• pregnancy and lactating
• History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS S Raffaele

Milan, 20132, Italy

Location

Related Publications (3)

• Reni M, Zanon S, Peretti U, Chiaravalli M, Barone D, Pircher C, Balzano G, Macchini M, Romi S, Gritti E, Mazza E, Nicoletti R, Doglioni C, Falconi M, Gianni L. Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):691-697. doi: 10.1016/S2468-1253(18)30196-1. Epub 2018 Jul 7.

  PMID: 30220407 DERIVED

• Reni M, Zanon S, Balzano G, Passoni P, Pircher C, Chiaravalli M, Fugazza C, Ceraulo D, Nicoletti R, Arcidiacono PG, Macchini M, Peretti U, Castoldi R, Doglioni C, Falconi M, Partelli S, Gianni L. A randomised phase 2 trial of nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in locally advanced or borderline resectable pancreatic adenocarcinoma. Eur J Cancer. 2018 Oct;102:95-102. doi: 10.1016/j.ejca.2018.07.007. Epub 2018 Aug 24.

  PMID: 30149366 DERIVED

• Reni M, Balzano G, Zanon S, Passoni P, Nicoletti R, Arcidiacono PG, Pepe G, Doglioni C, Fugazza C, Ceraulo D, Falconi M, Gianni L. Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma. Br J Cancer. 2016 Jul 26;115(3):290-6. doi: 10.1038/bjc.2016.209. Epub 2016 Jul 12.

  PMID: 27404453 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Disease

Interventions

Cisplatin; Capecitabine; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Michele Reni, MD

  IRCCS S RAFFAELE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 4, 2012
• First Posted: November 21, 2012
• Study Start: November 1, 2012
• Primary Completion: February 1, 2017
• Study Completion: August 1, 2017
• Last Updated: September 1, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)